This project will continue our studies of the calcitonin-like peptide described originally by us and subsequently by others in the pituitary glands of many species. We have pursued systematic multifaceted studies of the biochemistry, immunochemistry, and secretion of the peptide and its relationship to calcitonin in the thyroid and to other peptides, notably the proopiomelanocortin precursor. We have developed and optimized a purification strategy for the peptide using high performance liquid chromatography. Finally, we have purified sufficient amounts of the peptide to the point of a single peak by HPLC. Intracerebral administration of calcitonin produces diverse effects on CNS functions such as sensory perception and appetite and on pituitary secretion. Thus, CNS calcitonin may be an important new neuropeptide. In the continuation of this work we will complete the structural characterization of the peptide from porcine pituitaries by microsequencing and other methods. We shall pursue the purification of the calcitonin-like pituitary peptide from human pituitary glands or a second species and initiate work on the purification of human calcitonin-like peptides from the thyroids of artiodactyls and ultimobranchial glands of teleosts. The biological activity of highly purified calcitonin-like pituitary peptide will be evaluated by hypocalcemic and in vitro bioassays. The effects of calcitonins on pituitary function will be localized at the anatomical and ultrastructural level. Further studies of secretion and regulation of pituitary calcitonin content will be performed and the regulation of calcitonin receptors in the brain will be studied. These studies should help to further define the role of CNS calcitonin in neurobiology.